Title
Author(s)
Citation
Issue Date
Asymmetric Michael addition of aldehydes to nitroalkenes
using a primary amino acid lithium salt
Yoshida, Masanori; Sato, Atsushi; Hara, Shoji
Organic & Biomolecular Chemistry, 8(13): 3031-3036
2010-06-28
DOI
Doc URL
http://hdl.handle.net/2115/45249
Right
Org. Biomol. Chem., 2010, 8, 3031-3036 - Reproduced by
permission of The Royal Society of Chemistry (RSC)
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article (author version)
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Electronic Supplementary Information
Asymmetric Michael addition of aldehydes to nitroalkenes using a primary amino acid lithium salt
Masanori Yoshida,* Atsushi Sato and Shoji Hara
Division of Chemical Process Engineering, Graduate School of Engineering,
Hokkaido University, Sapporo 060-8628 Japan.
Fax: +81 11 706 6557; Tel:+81 11 706 6557;
E-mail: myoshida@eng.hokudai.ac.jp
Contents
(A) General comments
(B) Compound characterization data of Michael adducts
(C) References
(A) General comments
IR spectra were recorded using a JASCO FT/IR-5300 or FT/IR-410 spectrometer. 1H NMR
(400 MHz) and
13C
NMR (100 MHz) spectra were recorded on a JEOL JNM-A400II or
ECX-400P FT NMR. Chemical shifts, δ are referred to TMS. EI and ESI high-resolution
mass spectra were measured on a JEOL JMS-700TZ or JMS-T100LP spectrometer. Optical
rotation was measured by a JASCO DIP-360 or P-2200. Melting points are measured by
Yanagimoto micro melting point apparatus and are uncorrected. HPLC was carried out
using a JASCO PU-2089 Plus intelligent pump and a UV-2075 Plus UV detector.
(B) Compound characterization data of the Michael adducts
(S)-2,2-Dimethyl-4-nitro-3-phenylbutanal (3a)
The enantioselectivity was determined by HPLC analysis [98% ee,
DAICEL CHIRALCEL OD-H, 10% isopropanol/hexane, 1.0 mL/min, 254
O
H
NO2
nm; tr(major enantiomer) = 33.5 min, tr(minor enantiomer) = 21.6 min].
The absolute configuration was determined by comparison of the optical
rotation with that of the literature.1 [α]26D = –4.9° (c = 1.0, CHCl3), light yellow oil,
δH(CDCl3) 1.01 (3H, s), 1.14 (3H, s), 3.79 (1H, dd, J 4.2, 11.3 Hz), 4.69 (1H, dd, J 4.2, 13.1
Hz), 4.86 (1H, dd, J 11.3, 13.1 Hz), 7.20-7.21 (2H, m), 7.30-7.36 (3H, m), 9.53 (1H, s);
δC(CDCl3) 18.7, 21.5, 48.1, 48.3, 76.2, 128.0, 128.5, 128.9, 135.3, 204.2; ν(neat)/cm-1 3065,
3034, 2975, 2934, 2878, 2820, 2720, 1725, 1603, 1555, 1495, 1468, 1456, 1435, 1379, 1337,
1314, 1206, 1159, 1144, 1090, 1032, 1005, 976, 912, 883, 831, 804, 781, 750, 706, 648; [HR
EI-MS: Calc. for C12H15NO3 (M): 221.1052. Found: M+, 221.1044].
10000
1
Intensity [µV]
2
5000
0
20.0 22.0
24.0
26.0
30.0
32.0
28.0
Retention Time [min]
34.0
36.0
38.0 40.0
34.0
36.0
38.0 40.0
2
Intensity [µV]
15000
10000
5000
0
1
20.0 22.0
24.0
26.0
28.0
30.0
32.0
Retention Time [min]
(S)-2,2-Dimethyl-3-(4-methoxyphenyl)-4-nitrobutanal (3b)
OMe
The enantioselectivity was determined by HPLC analysis [98% ee,
DAICEL CHIRALCEL OD-H, 10% isopropanol/hexane, 1.0 mL/min, 254
O
H
nm; tr(major enantiomer) = 35.6 min, tr(minor enantiomer) = 22.1 min].
NO2 The absolute configuration was determined by comparison of the optical
rotation with that of the literature.1f,g
[α]26D = +1.7° (c = 1.0, CHCl3), white solid, Mp. 58-59 °C, δH(CDCl3) 1.00 (3H, s), 1.13 (3H, s),
3.73 (1H, dd, J 4.2, 11.5 Hz), 3.79 (3H, s), 4.66 (1H, dd, J 4.2, 12.8 Hz), 4.81 (1H, dd, J 11.5,
12.8 Hz), 6.86 (2H, d, J 8.7 Hz), 7.11 (2H, d, J 8.7 Hz), 9.53 (1H, s); δC(CDCl3) 18.7, 21.4,
47.7, 48.2, 55.1, 76.4, 113.9, 126.9, 130.0, 159.2, 204.3; ν(KBr)/cm-1 2976, 2919, 2841, 2718,
1725, 1611, 1582, 1553, 1516, 1468, 1441, 1379, 1290, 1250, 1188, 1119, 1028, 889, 839, 812,
747, 635; [HR EI-MS: Calc. for C13H17NO4 (M): 251.1158. Found: M+, 251.1152].
1
2
Intensity [µV]
1000
500
20.0 22.0
24.0
26.0
28.0
30.0
32.0
Retention Time [min]
34.0
36.0
38.0 40.0
36.0
38.0 40.0
2
Intensity [µV]
30000
20000
10000
1
0
20.0 22.0
24.0
26.0
28.0
30.0
32.0
Retention Time [min]
34.0
(S)-3-(4-Bromophenyl)-2,2-dimethyl-4-nitrobutanal (3c)
Br
The enantioselectivity was determined by HPLC analysis [99% ee,
DAICEL CHIRALCEL OD-H, 10% isopropanol/hexane, 1.0 mL/min, 254
O
H
nm; tr(major enantiomer) = 38.2 min, tr(minor enantiomer) = 24.0 min].
NO2 The absolute configuration was determined by comparison of the optical
rotation with that of the literature.2 [α]26D = –3.3° (c = 1.0, CHCl3), white
solid, Mp. 86-87 °C, δH(CDCl3) 1.02 (3H, s), 1.13 (3H, s), 3.76 (1H, dd, J 4.2, 11.3 Hz), 4.69
(1H, dd, J 4.2, 13.2 Hz), 4.82 (1H, dd, J 11.3, 13.2 Hz), 7.09 (2H, d, J 8.6 Hz), 7.47 (2H, d, J
8.6 Hz), 9.50 (1H, s); δC(CDCl3) 18.8, 21.6, 47.8, 48.0, 75.9, 122.1, 130.6, 131.8, 134.3, 203.7;
ν(KBr)/cm-1 3030, 2973, 2934, 2874, 2818, 2718, 1728, 1559, 1487, 1468, 1441, 1410, 1381,
1350, 1306, 1206, 1144, 1113, 1074, 1009, 889, 845, 781, 721, 702, 664; [HR EI-MS: Calc. for
C12H14BrNO3 (M ): 299.0157. Found: M+, 299.0145].
1
4000
Intensity [µV]
2
2000
0
20.0
25.0
30.0
35.0
Retention Time [min]
40.0
45.0
40.0
45.0
2
Intensity [µV]
10000
5000
1
0
20.0
25.0
30.0
35.0
Retention Time [min]
3-(3-Bromophenyl)-2,2-dimethyl-4-nitrobutanal (3d)3
Br
DAICEL CHIRALCEL OD-H, 10% ethanol/hexane, 1.0 mL/min, 209 nm;
O
H
The enantioselectivity was determined by HPLC analysis [92% ee,
*
NO2
tr(major enantiomer) = 29.3 min, tr(minor enantiomer) = 18.3 min]. [α]23D
= +4.0° (c = 1.0, CHCl3), yellow oil, δH(CDCl3) 1.02 (3H, s), 1.14 (3H, s),
3.77 (1H, dd, J 4.0, 11.3 Hz), 4.69 (1H, dd, J 4.0, 13.2 Hz), 4.83 (1H, dd, J 11.3, 13.2 Hz),
7.14-7.24 (2H, m), 7.36 (1H, s), 7.43-7.46 (1H, m), 9.50 (1H, s); δC(CDCl3) 18.8, 21.8, 47.9,
48.2, 76.0, 122.8, 127.7, 130.2, 131.3, 132.1, 137.9, 203.7; ν(neat)/cm-1 3073, 2975, 2936,
2877, 2812, 2710, 1727, 1558, 1475, 1434, 1380, 1348, 1295, 1213, 1141, 1067, 997, 978, 881,
840, 811, 783, 702, 646; [HR ESI-MS: Calc. for C12H14BrNNaO3 (M+Na): 322.0055. Found:
M++Na, 322.0044].
150000
1
100000
Intensity [µV]
2
50000
0
18.0
20.0
22.0
24.0
26.0
Retention Time [min]
28.0
30.0
32.0
30.0
32.0
2
Intensity [µV]
200000
100000
1
0
18.0
20.0
22.0
24.0
26.0
Retention Time [min]
28.0
3-(2-Bromophenyl)-2,2-dimethyl-4-nitrobutanal (3e)3
The enantioselectivity was determined by HPLC analysis [92% ee,
O
H
*
Br
NO2
DAICEL CHIRALCEL OD-H, 10% isopropanol/hexane, 1.0 mL/min, 209
nm; tr(major enantiomer) = 47.0 min, tr(minor enantiomer) = 16.4 min].
[α]23D = –13.0° (c = 1.0, CHCl3), orange solid, Mp. 60-61 °C, δH(CDCl3) 1.10
(3H, s), 1.18 (3H, s), 4.63 (1H, dd, J 4.1, 11.4 Hz), 4.72 (1H, dd, J 4.1, 13.3 Hz), 4.84 (1H, dd,
J 11.4, 13.3 Hz), 7.14-7.18 (1H, m), 7.26-7.35 (2H, m), 7.61-7.63 (1H, m), 9.50 (1H, s);
δC(CDCl3) 18.7, 20.9, 45.2, 49.1, 76.4, 127.1, 127.8, 128.3, 129.4, 133.9, 135.4, 203.8;
ν(KBr)/cm-1 3068, 3033, 2970, 2935, 2874, 2818, 2725, 1730, 1554, 1472, 1438, 1402, 1379,
1273, 1201, 1065, 1024, 910, 891, 801, 752, 723, 662, 625; [HR ESI-MS: Calc. for
C12H14BrNNaO3 (M+Na): 322.0055. Found: M++Na, 322.0052].
1
150000
Intensity [µV]
100000
2
50000
0
15.0
20.0
25.0
30.0
35.0
Retention Time [min]
40.0
45.0
50.0
2
Intensity [µV]
150000
100000
50000
1
0
15.0
20.0
25.0
30.0
35.0
Retention Time [min]
40.0
45.0
50.0
2,2-Dimethyl-3-(4-fluorophenyl)-4-nitrobutanal (3f)
The enantioselectivity was determined by HPLC analysis [99% ee,
F
DAICEL CHIRALCEL OD-H, 10% isopropanol/hexane, 1.0 mL/min, 254
nm; tr(major enantiomer) = 33.9 min, tr(minor enantiomer) = 17.4 min].
O
H
*
26
NO2 [α] D = –1.5° (c = 1.0, CHCl3), light yellow oil, δH(CDCl3) 1.01 (3H, s), 1.13
(3H, s), 3.78 (1H, dd, J 4.2, 11.5 Hz), 4.69 (1H, dd, J 4.2, 13.1 Hz), 4.82 (1H,
dd, J 11.5, 13.1 Hz), 7.01-7.06 (2H, m), 7.17-7.21 (2H, m), 9.51 (1H, s); δC(CDCl3) 18.7, 21.5,
47.6, 48.1, 76.2, 115.6 (d, J 21.5 Hz), 130.5 (d, J 8.1 Hz), 131.0 (d, J 3.3 Hz), 162.3 (d, J 247.0
Hz), 203.9; ν(neat)/cm-1 3045, 2976, 2936, 2878, 2820, 2722, 1725, 1605, 1555, 1512, 1470,
1437, 1379, 1304, 1229, 1165, 1105, 1017, 883, 843, 750, 689, 646; [HR EI-MS: Calc. for
C12H14FNO3 (M): 239.0958. Found: M+, 239.0954].
Intensity [µV]
10000
1
2
5000
0
15.0
20.0
25.0
30.0
Retention Time [min]
35.0
40.0
35.0
40.0
2
Intensity [µV]
20000
10000
1
0
15.0
20.0
25.0
30.0
Retention Time [min]
Methyl 4-(3,3-dimethyl-1-nitro-4-oxobutan-2-yl)benzoate (3g)
COOMe
The enantioselectivity was determined by HPLC analysis [96% ee,
DAICEL CHIRALPAK AD-H, 20% isopropanol/hexane, 1.0 mL/min, 209
nm; tr(major enantiomer) = 13.5 min, tr(minor enantiomer) = 11.5 min].
O
H
*
23
NO2 [α] D = +7.9° (c = 1.0, CHCl3), white solid, Mp. 88-89 °C, δH(CDCl3) 1.01
(3H, s), 1.14 (3H, s), 3.86 (1H, dd, J 4.1, 11.4 Hz), 3.92 (3H, s), 4.73 (1H, dd,
J 4.1, 13.2 Hz), 4.89 (1H, dd, J 11.4, 13.2 Hz), 7.30 (2H, d, J 8.2 Hz), 8.01 (2H, d, J 8.2 Hz),
9.52 (1H, s); δC(CDCl3) 18.9, 21.8, 48.1, 48.2, 52.2, 75.9, 129.2, 129.9, 130.1, 140.7, 166.5,
203.6; ν(neat)/cm-1 3101, 3060, 3031, 2975, 2952, 2816, 2723, 1723, 1611, 1553, 1436, 1378,
1284, 1192, 1112, 1020, 962, 900, 862, 797, 762, 710, 630; [HR ESI-MS: Calc. for
C14H17NNaO5 (M+Na): 302.1004. Found: M++Na, 302.1007].
1
400000
2
Intensity [µV]
300000
200000
100000
0
10.0
10.5
11.0
11.5
12.0
12.5
13.0
Retention Time [min]
13.5
14.0
14.5
15.0
14.0
14.5
15.0
2
800000
Intensity [µV]
600000
400000
200000
1
0
10.0
10.5
11.0
11.5
12.0
12.5
13.0
Retention Time [min]
13.5
(S)-2,2-Dimethyl-4-nitro-3-(4-nitrophenyl)butanal (3h)
NO2
The enantioselectivity was determined by HPLC analysis [97% ee,
DAICEL CHIRALPAK AD-H, 20% isopropanol/hexane, 1.0 mL/min, 209
O
H
nm; tr(major enantiomer) = 20.6 min, tr(minor enantiomer) = 15.5 min].
NO2 The absolute configuration was determined by comparison of the optical
rotation with that of the literature.1f,g [α]23D = –7.6° (c = 1.0, CHCl3),
orange solid, Mp. 57-59 °C, δH(CDCl3) 1.06 (3H, s), 1.16 (3H, s), 3.93 (1H, dd, J 4.1, 11.4 Hz),
4.78 (1H, dd, J 4.1, 13.7 Hz), 4.92 (1H, dd, J 11.4, 13.7 Hz), 7.43 (2H, d, J 8.7 Hz), 8.22 (2H,
d, J 8.7 Hz), 9.49 (1H, s); δC(CDCl3) 19.1, 21.9, 48.1, 48.2, 75.8, 123.8, 130.1, 143.3, 147.7,
203.1; ν(KBr)/cm-1 3112, 3083, 2974, 2939, 2876, 2825, 2719, 1729, 1606, 1561, 1469, 1440,
1348, 1205, 1187, 1110, 1012, 887, 859, 747, 704, 656.
1
2
Intensity [µV]
200000
100000
0
13.0
14.0
15.0
16.0
17.0
18.0
19.0
Retention Time [min]
20.0
21.0
22.0
23.0
20.0
21.0
22.0
23.0
Intensity [µV]
2
100000
1
0
13.0
14.0
15.0
16.0
17.0
18.0
19.0
Retention Time [min]
(S)-2,2-Dimethyl-3-(furan-2-yl)-4-nitrobutanal (3i)
The enantioselectivity was determined by HPLC analysis [96% ee,
O
H
DAICEL CHIRALPAK AD-H, 1% isopropanol/hexane, 1.0 mL/min, 254
O
NO2
nm; tr(major enantiomer) = 21.9 min, tr(minor enantiomer) = 17.0 min].
The absolute configuration was determined by comparison of the optical
rotation with that of the literature.1f,g,2a
[α]26D = +20.2° (c = 1.0, CHCl3), light yellow oil, δH(CDCl3) 1.05 (3H, s), 1.18 (3H, s), 3.92
(1H, dd, J 3.9, 11.0 Hz), 4.59 (1H, dd, J 3.9, 12.8 Hz), 4.76 (1H, dd, J 11.0, 12.8 Hz), 6.22 (1H,
d, J 3.2 Hz), 6.31 (1H, dd, J 1.6, 3.2 Hz), 7.38 (1H, d, J 1.6 Hz), 9.51 (1H, s); δC(CDCl3) 19.0,
21.1, 42.2, 48.1, 74.8, 109.6, 110.4, 142.7, 149.7, 203.4; ν(neat)/cm-1 3151, 3123, 2975, 2935,
2877, 2821, 2720, 1772, 1727, 1556, 1505, 1469, 1433, 1377, 1344, 1294, 1181, 1148, 1078,
1016, 973, 915, 886, 819, 742, 700, 599; [HR EI-MS: Calc. for C10H13NO4 (M): 211.0845.
Found: M+, 211.0853].
1
2
Intensity [µV]
10000
5000
0
17.0
18.0
19.0
20.0
21.0
Retention Time [min]
22.0
23.0
2
Intensity [µV]
30000
20000
10000
1
0
16.0
17.0
18.0
19.0
20.0
Retention Time [min]
21.0
22.0
(S)-2,2-Dimethyl-4-nitro-3-(thiophen-2-yl)butanal (3j)
The enantioselectivity was determined by HPLC analysis [95% ee,
O
H
DAICEL CHIRALPAK AD-H, 10% isopropanol/hexane, 0.5 mL/min, 209
S
NO2
nm; tr(major enantiomer) = 19.5 min, tr(minor enantiomer) = 18.3 min].
The absolute configuration was determined by comparison of the optical
rotation with that of the literature.1f,g [α]23D = –5.1° (c = 1.0, CHCl3), light yellow oil,
δH(CDCl3) 1.09 (3H, s), 1.21 (3H, s), 4.14 (1H, dd, J 4.3, 10.6 Hz), 4.66 (1H, dd, J 4.3, 12.8
Hz), 4.73 (1H, dd, J 10.6, 12.8 Hz), 6.93 (1H, d, J 3.6 Hz), 6.97 (1H, dd, J 3.6, 5.0 Hz), 7.25
(1H, d, J 5.0 Hz), 9.54 (1H, s); δC(CDCl3) 18.9, 21.5, 44.0, 48.3, 77.8, 125.5, 126.9, 127.9,
137.8, 203.6; ν(neat)/cm-1 3110, 2974, 2930, 2880, 2819, 2719, 1724, 1556, 1468, 1434, 1379,
1341, 1249, 1206, 1162, 1064, 883, 851, 706.
1
2
300000
Intensity [µV]
200000
100000
0
17.0
17.5
18.0
18.5
19.0
Retention Time [min]
19.5
20.0
20.5
21.0
20.0
20.5
21.0
2
Intensity [µV]
1000000
500000
1
0
17.0
17.5
18.0
18.5
19.0
Retention Time [min]
19.5
2,2-Dimethyl-4-nitro-3-(3-pyridyl)butanal (3k)
The enantioselectivity was determined by HPLC analysis [93% ee,
N
DAICEL CHIRALPAK AD-H, 20% isopropanol/hexane, 1.0 mL/min, 209
O
H
*
NO2
nm; tr(major enantiomer) = 11.1 min, tr(minor enantiomer) = 13.0 min].
[α]23D = +9.9° (c = 1.0, CHCl3), orange oil, δH(CDCl3) 1.05 (3H, s), 1.15 (3H,
s), 3.82 (1H, dd, J 4.1, 11.4 Hz), 4.75 (1H, dd, J 4.1, 13.7 Hz), 4.88 (1H, dd, J 11.4, 13.7 Hz),
7.27-7.31 (1H, m), 7.57-7.60 (1H, m), 8.51-8.52 (1H, m), 8.56-8.58 (1H, m), 9.51 (1H, s);
δC(CDCl3) 18.9, 21.8, 46.0, 48.2, 75.7, 123.5, 131.4, 136.1, 149.6, 150.6, 203.4; ν(neat)/cm-1
3420, 2975, 2934, 2872, 2822, 2722, 1725, 1555, 1469, 1430, 1379, 1186, 1027, 883, 822,
718; [HR ESI-MS: Calc. for C11H15N2O3 (M+H): 223.1083. Found: M++H, 223.1081].
1
2
Intensity [µV]
400000
200000
0
10.0
10.5
11.5
11.0
12.0
Retention Time [min]
12.5
13.0
13.5
14.0
13.5
14.0
Intensity [µV]
1
500000
2
0
10.0
10.5
11.0
11.5
12.0
Retention Time [min]
12.5
13.0
(S)-(E)-2,2-Dimethyl-3-(nitromethyl)-5-phenylpent-4-enal (3l)
The enantioselectivity was determined by HPLC analysis [96% ee,
DAICEL CHIRALPAK AD-H, 5% ethanol/hexane, 1.0 mL/min, 209 nm;
O
H
tr(major enantiomer) = 32.8 min, tr(minor enantiomer) = 25.9 min]. The
NO2 absolute configuration was determined by comparison of the optical
rotation with that of the literature.1f,g [α]28D = +22.6° (c = 1.0, CHCl3),
yellow oil, δH(CDCl3) 1.167 (3H, s), 1.172 (3H, s), 3.27 (1H, ddd, J 4.1, 9.9, 10.4 Hz), 4.46
(1H, dd, J 10.4, 12.2 Hz), 4.52 (1H, dd, J 4.1, 12.2 Hz), 6.02 (1H, dd, J 9.9, 15.9 Hz), 6.53
(1H, d, J 15.9 Hz), 7.27-7.35 (5H, m), 9.51 (1H, s); δC(CDCl3) 19.0, 20.9, 47.2, 47.7, 76.6,
122.8, 126.5, 128.2, 128.6, 135.9, 136.3, 203.7; ν(neat)/cm-1 3060, 3028, 2974, 2932, 2875,
2817, 2716, 1723, 1554, 1494, 1468, 1449, 1434, 1380, 1200, 1075, 972, 887, 749, 694.
1
2
Intensity [µV]
400000
200000
0
24.0
26.0
28.0
30.0
Retention Time [min]
32.0
34.0
2
300000
Intensity [µV]
200000
100000
1
0
24.0
26.0
28.0
30.0
Retention Time [min]
32.0
34.0
(E)-2,2-Dimethyl-3-(nitromethyl)oct-4-enal (3m)
The enantioselectivity was determined by HPLC analysis [94% ee,
DAICEL CHIRALCEL OD-H, 20% isopropanol/hexane, 1.0 mL/min, 209
O
H
*
NO2 nm; tr(major enantiomer) = 10.0 min, tr(minor enantiomer) = 6.1 min].
[α]28D = –20.3° (c = 1.0, CHCl3), colorless oil, δH(CDCl3) 0.86 (3H, t, J 7.3
Hz), 1.09 (6H, s), 1.31-1.41 (2H, m), 1.98 (2H, dt, J 6.8, 7.3 Hz), 3.05 (1H, ddd, J 3.9, 9.8,
10.7 Hz), 4.30 (1H, dd, J 10.7, 11.7 Hz), 4.42 (1H, dd, J 3.9, 11.7 Hz), 5.26 (1H, dd, J 9.8,
15.1 Hz), 5.59 (1H, dt, J 6.8, 15.1 Hz), 9.47 (1H, s); δC(CDCl3) 13.4, 18.8, 20.5, 22.1, 34.5,
46.9, 47.3, 76.9, 123.2, 138.1, 204.0; ν(neat)/cm-1 2963, 2931, 2873, 2714, 1728, 1556, 1466,
1436, 1380, 1339, 1202, 1056, 934, 887, 780, 718, 634.
300000
1
200000
Intensity [µV]
2
100000
0
5.5
6.0
6.5
7.0
7.5
8.5
8.0
Retention Time [min]
9.0
9.5
10.0
10.5
11.0
10.5
11.0
2
Intensity [µV]
40000
20000
1
0
5.5
6.0
6.5
7.0
7.5
8.0
8.5
Retention Time [min]
9.0
9.5
10.0
3-Cyclohexyl-2,2-dimethyl-4-nitrobutanal (3n)
The enantioselectivity was determined by HPLC analysis [88% ee,
DAICEL CHIRALCEL OD-H, 5% isopropanol/hexane, 1.0 mL/min, 210
O
H
*
NO2 nm; tr(major enantiomer) = 9.3 min, tr(minor enantiomer) = 7.6 min].
[α]26D = –11.3° (c = 1.0, CHCl3), colorless oil, δH(CDCl3) 0.90-1.29 (11H, m),
1.47-1.76 (6H, m), 2.57-2.61 (1H, m), 4.40 (1H, dd, J 5.0, 14.0 Hz), 4.48 (1H, dd, J 6.5, 14.0
Hz), 9.51 (1H, s); δC(CDCl3) 19.2, 20.5, 25.4, 25.9, 26.3, 29.0, 32.9, 38.2, 46.8, 48.7, 73.5,
203.9; ν(neat)/cm-1 2929, 2855, 2709, 1724, 1554, 1449, 1373, 1308, 1249, 1103, 1025, 893,
841, 760, 704.
40000
Intensity [µV]
30000
20000
10000
0
7.0
7.5
8.0
8.5
9.0
9.5
Retention Time [min]
10.0
10.5
11.0
7.0
7.5
8.0
8.5
9.0
9.5
Retention Time [min]
10.0
10.5
11.0
Intensity [µV]
40000
20000
0
(S)-2,2-Dimethyl-3-(nitromethyl)-5-phenylpentanal (3o)
The enantioselectivity was determined by HPLC analysis [88% ee,
DAICEL CHIRALPAK AD-H, 1% isopropanol/hexane, 1.0 mL/min, 254
O
H
NO2
nm; tr(major enantiomer) = 16.1 min, tr(minor enantiomer) = 17.4 min].
The absolute configuration was determined by comparison of the
optical rotation with that of the literature.3 [α]26D = –22.5° (c = 1.0, CHCl3), colorless oil,
δH(CDCl3) 1.07 (6H, s), 1.57-1.77 (2H, m), 2.54-2.65 (2H, m), 2.68-2.76 (1H, m), 4.35 (1H, dd,
J 6.5, 13.1 Hz), 4.49 (1H, dd, J 5.1, 13.1 Hz), 7.14-7.31 (5H, m), 9.37 (1H, s); δC(CDCl3) 18.0,
19.3, 31.1, 33.6, 40.6, 48.3, 76.2, 125.9, 127.9, 128.1, 140.2, 203.4; ν(neat)/cm-1 3062, 3028,
2971, 2949, 2871, 2817, 2711, 1725, 1603, 1555, 1496, 1455, 1381, 1211, 1091, 1030, 885,
751, 701; [HR ESI-MS: Calc. for C14H20NO3 (M+H): 250.1443. Found: M++H, 250.1424].
1
2
Intensity [µV]
3000
2000
1000
0
15.0
15.5
16.0
16.5
Retention Time [min]
17.0
17.5
18.0
17.5
18.0
18.5
15000
1
Intensity [µV]
10000
5000
2
0
15.5
16.0
16.5
17.0
Retention Time [min]
2,2,3-Trimethyl-4-nitrobutanal (3p)
The enantioselectivity was determined by HPLC analysis [91% ee,
O
H
[α]26D
*
NO2 DAICEL CHIRALCEL OD-H, 20% isopropanol/hexane, 1.0 mL/min, 209
nm; tr(major enantiomer) = 10.5 min, tr(minor enantiomer) = 8.4 min].
= –20.0° (c = 1.0, CHCl3), colorless oil, δH(CDCl3) 1.03 (3H, d, J 6.8 Hz), 1.09 (3H, s),
1.10 (3H, s), 2.65-2.71 (1H, m), 4.17 (1H, dd, J 10.2, 12.2 Hz), 4.44 (1H, dd, J 3.9, 12.2 Hz),
9.47 (1H, s); δC(CDCl3) 12.9, 18.7, 19.1, 36.5, 47.6, 78.3, 203.9; ν(neat)/cm-1 2977, 2942, 2883,
2820, 2716, 1725, 1556, 1469, 1436, 1380, 1241, 1128, 1050, 885, 847, 778, 717.
1
400000
2
Intensity [µV]
300000
200000
100000
0
7.5
8.0
8.5
9.0
9.5
10.0
Retention Time [min]
10.5
11.0
11.5
12.0
11.0
11.5
12.0
2
400000
Intensity [µV]
300000
200000
100000
1
0
7.5
8.0
8.5
9.0
9.5
10.0
Retention Time [min]
10.5
2-Methyl-4-nitro-2,3-diphenylbutanal (3q)2a
The enantioselectivity was determined by HPLC analysis [10% ee,
DAICEL CHIRALCEL OD-H, 2% isopropanol/hexanes, 1.2 mL/min, 209
O
H
*
*
tr(major enantiomer, anti) = 30.0 min, tr(minor enantiomer, syn) =
33.6 min, tr(minor enantiomer, anti) = 43.1 min, tr(major enantiomer, syn)
NO2 nm;
= 47.4 min]. white solid, Mp. 98-100 °C, Characterization data for syn
isomer: δH(CDCl3): 1.52 (3H, s), 4.20 (1H, dd, J 3.9, 11.2 Hz), 4.86 (1H, dd, J 3.9, 13.1 Hz),
5.03 (1H, dd, J 11.2, 13.1 Hz), 6.92-6.94 (2H, m), 7.05-7.07 (2H, m), 7.10-7.14 (3H, m),
7.25-7.33 (3H, m), 9.56 (1H, s); δC(CDCl3) 16.7, 49.6, 56.6, 76.1, 127.2, 127.6, 128.0, 128.1,
129.0, 129.2, 135.3, 137.2, 201.0; ν(KBr)/cm-1 3086, 3065, 3028, 3000, 2980, 2921, 2827,
2724, 1962, 1886, 1811, 1718, 1600, 1557, 1494, 1455, 1430, 1379, 1205, 1097, 1078, 1029,
1003, 992, 919, 903, 865, 783, 747, 700.
200000
2
Intensity [µV]
4
100000
1
3
0
25.0
30.0
35.0
40.0
Retention Time [min]
45.0
50.0
1
150000
2
Intensity [µV]
100000
50000
0
25.0
30.0
35.0
40.0
Retention Time [min]
45.0
50.0
2-Methyl-2-(2-nitro-1-phenylethyl)pentanal (3r)1c,d
The enantioselectivity was determined by HPLC analysis [22% ee,
DAICEL CHIRALCEL OD-H, 4% isopropanol/hexanes, 1.0 mL/min, 254
O
H
*
*
NO2
nm; tr(minor enantiomer, anti) = 21.9 min, tr(minor enantiomer, syn) =
28.7 min, tr(major enantiomer, syn) = 39.0 min, tr(major enantiomer, anti)
= 44.0 min]. light yellow oil, δH(CDCl3): 0.84 (syn) and 0.90 (anti) (3H, t, J
6.8 Hz), 1.10 (anti) and 1.11 (syn) (3H, s), 1.15-1.66 (syn and anti) (4H, m), 3.77 (anti) and
3.79 (syn) (1H, dd, J 4.4, 11.2 and 3.9, 11.7 Hz), 4.62 (syn) and 4.76 (anti) (1H, dd, J 3.9,
13.2 and 4.4, 12.7 Hz), 4.84 (syn) and 4.85 (anti) (1H, dd, J 11.7, 13.2 and 11.2, 12.7 Hz),
7.16-7.21 (syn and anti) (2H, m), 7.28-7.35 (syn and anti) (3H, m), 9.52 (anti) and 9.54 (syn)
(1H, s); δC(CDCl3) 14.4 (syn), 14.6 (anti), 15.7 (syn), 17.0 (syn), 17.1 (anti), 17.3 (anti), 36.5
(anti), 37.5 (syn), 47.5 (syn), 49.1 (anti), 51.0 (anti), 51.6 (syn), 76.2 (anti), 76.7 (syn),
128.10 (syn), 128.13 (anti), 128.7 (syn and anti), 129.0 (anti), 129.1 (syn), 205.0 (anti), 205.4
(syn); ν(neat)/cm-1 3064, 3032, 2962, 2935, 2874, 2720, 1730, 1603, 1555, 1497, 1455, 1379,
1205, 1092, 1033, 1005, 982, 913, 851, 798, 751, 704.
2
3
Intensity [µV]
1
5000
4
0
20.0
25.0
35.0
Retention Time [min]
40.0
45.0
3
2
10000
Intensity [µV]
30.0
5000
4
1
0
25.0
30.0
35.0
Retention Time [min]
40.0
45.0
2-(2-nitro-1-phenylethyl)pentanal (3s)4
The enantioselectivity was determined by HPLC analysis [78% ee,
DAICEL CHIRALCEL OD-H, 15% isopropanol/hexanes, 1.0 mL/min, 254
O
H
*
*
NO2
nm; tr(major enantiomer, syn) = 18.1 min, tr(major enantiomer, anti) =
23.2 min, tr(minor enantiomer, syn) = 26.9 min, tr(minor enantiomer,
anti) = 43.0 min]. colorless oil, δH(CDCl3): 0.80 (syn) and 0.93 (anti) (3H, t,
J 6.2 Hz), 1.11-1.74 (syn and anti) (4H, m), 2.60-2.66 (anti) and 2.67-2.74 (syn) (1H, m),
3.75-3.83 (syn and anti) (1H, m), 4.65 (syn) and 4.75 (anti) (1H, dd, J 9.6, 12.7 and 9.1, 13.0
Hz), 4.71 (syn) and 4.82 (anti) (1H, dd, J 4.5, 12.7 and 6.2, 13.0 Hz), 7.16-7.19 (syn and anti)
(2H, m), 7.26-7.37 (syn and anti) (3H, m), 9.48 (anti) and 9.71 (syn) (1H, d, J 3.1 and 3.0
Hz); δC(CDCl3) 13.90 (syn), 13.95 (anti), 19.7 (syn), 20.3 (anti), 29.4 (syn), 29.6 (anti), 43.1
(syn), 44.4 (anti), 53.2 (anti), 53.8 (syn), 77.8 (anti), 78.4 (syn), 128.0 (syn), 128.1 (syn),
128.17 (anti), 128.19 (anti), 129.05 (anti), 129.08 (syn), 136.2 (anti), 136.7 (syn), 203.2 (anti),
203.3 (syn); ν(neat)/cm-1 3064, 3032, 2961, 2931, 2873, 2729, 1723, 1604, 1555, 1496, 1455,
1434, 1380, 1203, 1119, 1090, 990, 913, 844, 763, 703.
4000
3000
Intensity [µV]
1
2000
3
2
1000
4
0
20.0
25.0
30.0
35.0
Retention Time [min]
40.0
45.0
1
Intensity [µV]
10000
5000
2
3
4
0
20.0
25.0
30.0
35.0
Retention Time [min]
40.0
45.0
2-Methyl-2-(2-nitro-1-phenylethyl)pentanal (3t)5
The enantioselectivity was determined by HPLC analysis [89% ee,
DAICEL CHIRALCEL OD-H, 20% isopropanol/hexanes, 1.0 mL/min, 254
O
H
*
*
NO2 nm; tr(major enantiomer, syn) = 32.7 min, tr(major enantiomer, anti) =
38.2 min, tr(minor enantiomer, syn) = 48.8 min, tr(minor enantiomer,
anti) = 60.8 min]. yellow oil, δH(CDCl3): 2.73-3.15 (syn and anti) (4H, m),
3.80-3.87 (syn and anti) (1H, m), 4.70 (syn) and 4.74 (anti) (2H, dd, J 8.5,
12.7 and 6.1, 12.7 Hz), 6.97-6.98 (syn) and 7.02-7.40 (syn and anti) (10H, m), 9.56 (anti) and
9.71 (syn) (1H, d, J 2.0 and 2.4 Hz); δC(CDCl3) 33.6 (anti), 34.2 (syn), 43.4 (syn), 44.4 (anti),
54.4 (anti), 55.3 (syn), 77.6 (anti), 78.0 (syn), [(126.9, 127.0, 128.1, 128.3, 128.4, 128.7, 128.8,
128.9, 129.1, 129.3, 136.7, 137.2) (syn and anti)], 203.0 (syn), 203.1 (anti); ν(neat)/cm-1 3063,
3030, 2920, 2848, 2736, 1724, 1603, 1555, 1496, 1455, 1434, 1380, 1202, 1089, 1031, 913,
848, 759, 701.
1
6000
2
Intensity [µV]
4000
3
4
2000
0
30.0
35.0
40.0
45.0
50.0
Retention Time [min]
55.0
60.0
55.0
60.0
65.0
10000
Intensity [µV]
1
5000
3
2
4
0
30.0
35.0
40.0
45.0
50.0
Retention Time [min]
65.0
(2S,3R)-2-(Prop-2-yl)-3-phenylbutanal (3u)
The enantioselectivity was determined by HPLC analysis [89% ee,
DAICEL CHIRALPAK AS-H, 1% isopropanol/hexanes, 1.2 mL/min, 254
O
H
NO2
nm; tr(major enantiomer, syn) = 31.6 min, tr(minor enantiomer, syn) =
34.8 min, tr(major enantiomer, anti) = 41.5 min, tr(minor enantiomer,
anti) = 49.3 min]. The absolute configuration was determined by
comparison of the optical rotation with that of the literature.2a [α]22D = –41.9° (c = 0.8,
CHCl3), light yellow oil, Characterization data for syn isomer: δH(CDCl3): 0.88 (3H, d, J 6.8
Hz), 1.10 (3H, d, J 7.3 Hz), 1.68-1.76 (1H, m), 2.75-2.80 (1H, m), 3.87-3.93 (1H, m), 4.57 (1H,
dd, J 10.2, 12.7 Hz), 4.67 (1H, dd, J 4.4, 12.7 Hz), 7.18-7.20 (2H, m), 7.27-7.36 (3H, m), 9.93
(1H, d, J 2.4 Hz); δC(CDCl3) 16.9, 21.6, 27.9, 41.9, 58.7, 79.0, 127.9, 128.1, 129.1, 137.0,
204.3; ν(neat)/cm-1 3058, 3031, 2964, 2921, 2875, 2742, 1717, 1604, 1553, 1496, 1456, 1432,
1379, 1241, 1206, 1144, 1110, 1073, 1031, 994, 913, 815, 760, 703.
1
2
Intensity [µV]
4000
2000
3
4
0
32.0
34.0
36.0
38.0
40.0
42.0
Retention Time [min]
44.0
46.0
48.0 50.0
6000
Intensity [µV]
1
4000
2000
3
2
4
0
32.0
34.0
36.0
38.0
40.0
42.0
Retention Time [min]
44.0
46.0
48.0 50.0
(C) References
1
(a) Y. Xu, W. Zou, H. Sundén, I. Ibrahem, A. Córdova, Adv. Synth. Catal., 2006, 348, 418;
(b) Y. Hayashi, H. Gotoh, T. Hayashi, M. Shoji, Angew. Chem. Int. Ed., 2005, 44, 4212;
(c) N. Mase, R. Thayumanavan, F. Tanaka, C. F. Barbas, III, Org. Lett., 2004, 6, 2527;
(d) M. P. Lalonde, Y. Chen, E. N. Jacobsen, Angew. Chem. Int. Ed., 2006, 45, 6366; (e) S.
Mossé, A. Alexakis, Org. Lett., 2006, 8, 3577; (f) X.-J. Zhang, S.-P. Liu, X.-M. Li, M. Yan, A.
S. C. Chan, Chem. Commun., 2009, 833; (g) X.-J. Zhang, S.-P. Liu, J.-H. Lao, G.-J. Du, M. Yan, A.
S. C. Chan, Tetrahedron: Asymmetry, 2009, 20, 1451.
2
(a) S. H. McCooey, S. J. Connon, Org. Lett., 2007, 9, 599; (b) Y. Li, X.-Y. Liu, G. Zhao,
Tetrahedron: Asymmetry, 2006, 17, 2034.
3
4
5
C. Chang, S.-H. Li, R. J. Reddy, K. Chen, Adv. Synth. Catal., 2009, 351, 1273.
A. Alexakis, O. Andrey, Org. Lett., 2002, 4, 3611.
P. Kotrusz, S. Toma, H.-G. Schmalz, A. Adler, Eur. J. Org. Chem., 2004, 1577.